The specific aim of the research described in this proposal is to conduct indepth studies on two previously reported afebrile lizard species and to compare physiological events in previously reported febrile and afebrile lizard species. Because a number of lizard species have not demonstrated a fever response when challenged with pyrogen this proposal seeks to compare reported febrile and afebrile species to establish which physiological events are common to lizards in general and which are unique to potentially afebrile species. This research will determine (1) if some species of previously studied lizards truly are afebrile, in which case these species could be very important medically because they might lack certain biochemical and physiological processes, (2) if these "afebrile" lizards were exhibiting stress hyperthermia during previous studies, in which case the fever might have been masked, and (3) if these "afebrile" lizards were already exhibiting a fever due to a pre-existing bacterial infection which also would have masked any attempt to elicit an increase in Tb. Research on lizards outlined in this proposal will test a number of hypotheses. Hypothesis #1 is that previously reported afebrile lizards were not exhibiting stress hyperthermia. This will be tested first by maintaining potentially afebrile species in more complex environments and measuring mean selected body temperature (MSBT) by radiotelemetry instead of thermocouples, and second by using the beta adrenergic antagonist propranolol. Hypothesis #2 is that potentially afebrile species in general have low plasma iron levels under non-bacterial injection conditions and this level does not differ from that found after bacterial injection. Hypothesis #3 is that individuals of a potentially afebrile species can survive a live bacterial infection without demonstrating a fever and this relates to hypothesis #4 that artificially increasing MSBT and/or plasma iron level after live bacterial infection causes decreased survivorship in a potentially afebrile species. Hypothesis #5 states that previously reported afebrile lizard species were not exhibiting an elevated Tb because of an existing bacterial infection. Experiments will involve treating afebrile species with antibiotics, an antipyretic, and a cryogen in an attempt to reduce MSBT. Hypothesis #6 states that mammalian recombInant IL-lB and lL-6, and/or lizard endogenous pyrogen, do not affect Tb in a low MSBT regulating afebrile lizard species but do affect Tb in a high MSBT regulating febrile lizard species. Hypothesis #7, the last hypothesis, states that both afebrile and febrile species produce heat shock proteins and acute phase proteins after injection of endotoxin and IL-1B. The fact that fever is widespread among animals is no longer in doubt. However there are some lizard species that have not responded to putative pyrogen by exhibiting a fever and finding the answer why some species do not exhibit a fever could be medically relevant. If some species truly are afebrile then they could be used in an attempt to better understand the mechanism of the fever response.